Systemic vascular risk is a well-established contributor to late-life cognitive decline, yet the mechanism is not completely understood. We investigated whether neuroimaging-based measures of vascular injury could explain the effect of vascular risk on cognitive decline using longitudinal data from the Harvard Aging Brain Study.
We used the Framingham Heart Study cardiovascular disease risk score (FHS-CVD) as an index of vascular risk. We extracted white matter lesion from structural MRI (https://hypermapp3r.readthedocs.io/), PSMD from diffusion MRI (http://www.psmdmarker.com), and relative tracer delivery from PiB-PET (PiB-R1 as an index of blood flow). Global cognition was assessed using Preclinical Alzheimer Cognitive Composite (PACC).
We observed a significant effect of FHS-CVD on PACC change over time while PSMD and PiB-R1 mediating this effect in individuals with low amyloid burden. In contrast, tau burden (and not cerebrovascular injury markers) explained the effect of FHS-CVD on PACC change in the high amyloid group.
These results demonstrate that cerebrovascular injury largely explains the effect of systemic vascular risk on cognitive decline in older adults with lower amyloid burden suggesting mechanisms by which a higher systemic vascular risk impacts brain function.